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Seminar Recap – When Erythrocyte Biology and Mechanics Collide

Right now, hundreds of thousands of units of blood are in storage in blood banks across the country. But in terms of shelf life, they won’t last much longer than a gallon of orange juice.

Due to their short lifespan, the Red Cross requires for red blood cells to be used in 42 or fewer days after donation. In addition to a steady need for new or returning donors — the Red Cross relies on 9.2 million donors each year — this leads to the staggering costs associated with hosting nearly-constant blood drives.

But in recent months, researchers at the University of Rochester have been working on a way to use embryonic stem cells to generate red blood cells for clinical use.

James Palis, M.D.

James Palis, M.D., professor of pediatrics, hematology, and oncology in the Medical Center, and Rick Waugh, Ph.D., chair of the biomedical engineering department on River Campus, shared their research at an April seminar in Helen Wood Hall auditorium.

Problems of scale

A study from France that was published in the journal Blood in 2011 showed that red blood cells grown outside the body could be successfully infused back into a patient, and had lifespans on par with those of normal red blood cells.

“So there is a proof of principal that you can start with a source of progenitors, expand red cells and use them as a potential source of transfusion therapy,” said Palis.

Palis wanted to see if he could use embryonic stem cells and erythroid progenitors to generate self-renewing erythroblasts. After some successful preliminary results, Palis said that this type of red blood cell generation could be feasible on a larger scale.

However, each microliter (1/1,000,000th of a liter) of human blood contains 5 million red blood cells. This means that the average person has about 25 trillion red blood cells in their body at any one time.

Richard Waugh, Ph.D.

“So if, ultimately, this is going to serve as a source of blood, our biggest problem is one of scale,” said Palis. “Trying to synthesize that order of red cells is a mindboggling thought.”

Palis’s erythroblast cultures expand to a maximum concentration of about 2 million per 1 mL of media. This means that his cultures would need about 1,000 liters of media to generate just a single unit of blood.

“Clearly, that’s a crazy thought, so we said ‘It’s time for a bioengineer to help us figure out if it’s possible to grow more cells with less (media),” said Palis.

Significant challenges

Waugh stepped in, and worked with a team to create several bioreactor models that could fulfill this function.

Early attempts produced a decent number of cells, but a great majority of those cells had died in the process.

“So as you can see, there are some significant challenges when you try to go from standard culture dishes to something that can be operated without daily involvement of the technician, and without having to put together 1,000 units of media to produce a unit of blood,” said Waugh.

But Waugh said that the team has had some success using a new bioreactor that they’d recently developed. He didn’t give many details about it, saying that the team was planning to submit a patent on it, but one of Waugh’s students was able to use the bioreactor to grow red blood cells for three days, unattended, with 92 percent of the cells viable at the end of the process.

Waugh said that there is much work to be done, but he agreed with Palis that this method of red blood cell production could potentially be viable down the line.

“These self-renewing erythroblasts really show enormous promise for producing blood cells on a large scale,” said Waugh. “But we’re going to have to improve our bioreactors significantly if we’re going to get to the place where we’ll have some practical application.”